Anat Amital

Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation

Abstract:  Backgrounds:  The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure.

Use of Amplatzer device for endobronchial closure of bronchopleural fistulas.

Bronchopulmonary fistula (BPF) is associated with high morbidity and mortality. It occurs as an uncommon but often severe complication of pneumonectomy. BPF may be treated by a range of surgical and medical techniques, including chest drain, Eloesser muscle flap, omental flap, transsternal bronchial closure, thoracoplasty, and prolonged therapy with antibiotic regimens. The use of bronchoscopy has been reported for the delivery of biological glue, coils, covered stents, and sealants. In this work, we describe a novel method of BPF closure using the Amplatzer device, which is commonly used for transcatheter closure of atrial septal defects.

Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Objective. Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH. Methods. Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio. Results. Mean systolic pulmonary pressure was 70.5 ± 21.6 mm Hg (idiopathic-PAH) and 69.3 ± 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% ± 19.6% in healthy controls, 9.0% ± 21.5% in idiopathic-PAH, 20.1% ± 19.1% in scleroderma-PAH, and 24.4% ± 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 ± 0.25; idiopathic 1.84 ± 0.51; scleroderma 1.66 ± 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test. Conclusion. Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

OBJECTIVE Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. PATIENTS AND METHODS The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. RESULTS Mean follow-up for all patients was 25+/-10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57+/-15 vs 53+/-13 years, p=0.009), had increased BMI (26+/-5 vs 24+/-4, p=0.0001), shorter time from diagnosis to LTX (21+/-13 vs 28+/-18 months, p=0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p=0.72). CONCLUSIONS Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.

Development of malignancy following lung transplantation

Background. A substantial excess risk of certain malignancies has been demonstrated after organ transplantation. Immunosupressive treatment to prevent allograft rejection is probably the main cause. Methods. We reviewed retrospectively all medical records of the 121 patients that underwent lung and heart-lung transplantation from 1992 until December 2004. We compared our results to the International Society for Heart and Lung Transplantation (ISHLT) registry data and previous reports concerning lung transplantation. Results. 102 of the 121 patients survived for 3 months to 12 years. Malignancies developed in 16 patients, as follows: lymphoproliferative disorder in 3, Kaposis sarcoma in 3, other nonmelanoma skin cancers in 7, urinary bladder transitional cel carcinoma in 3, and colon cancer in 1. Patients with malignancy were older at transplantation than those without (mean ± SD, 54.1±7.8 vs. 49.5±14.2 years; P=0.03). Fourteen had smoked in the past. Four died of bronchiolitis obliterans. In comparison with the ISHLT, we observed more skin cancer and transitional cell carcinoma (12.8% vs. 0.7% and 3.8% vs. 0.03%, respectively) and a similar frequency of posttransplant lymphoproliferative disease. Conclusions. We conclude that malignancy is a common complication after lung transplantation. In Israel, which is sunny most of the year, skin cancers and transitional cell carcinoma of bladder are more common. Modification of the immunosuppression late posttransplantation may reduce the risk of cancer. Patients should also be counseled to avoid sun exposure and ensure adequate hydration.

Bronchoscopic balloon dilatation of tracheobronchial stenosis: long-term follow-up

OBJECTIVES Bronchoscopic balloon dilatation (BBD) has become a valuable tool in the treatment of tracheobronchial stenosis (TBS). The objective of this study was to assess the short- and long-term effects of BBD. METHODS A retrospective study that included all patients with confirmed, symptomatic stenosis, who underwent BBD between 2002 and 2008. A total of 92 BBD procedures were performed in 35 patients at our institute. Lung function studies were recorded for all patients before, immediately after and 1 month following the BBD. Long-term follow-up was for a mean of 33+/-4 months. RESULTS All patients had initial success, including increased airway dimensions and symptom relief. No complications were noted related to BBD. Forced expiratory volume after one second (FEV(1)) was significantly increased after BBD (10.5%, p=0.03). These effects persisted for at least 1 month. Long-term follow-up, however, demonstrated the need for stent placement in 25 of 35 patients (71%), 210+/-91 days after BBD. Ten of 35 patients died 456+/-119 days after BBD due to progression of primary disease; all deaths were unrelated to the BBD procedures. CONCLUSIONS BBD is a safe method that offers immediate symptomatic relief in both tracheal and bronchial stenosis. However, BBD is a temporary measure, as many patients will require definitive or additional treatment with laser or stent placement.

Lung cancer in lung transplant recipients: Experience of a tertiary hospital and literature review

BACKGROUND Lung transplantation is a viable therapy for patients with end-stage lung disease and is being increasingly performed worldwide. The incidence of lung cancer after lung transplantation has increased concomitantly, although data are still sparse. METHODS The computerized medical records of the Pulmonary Institute of a tertiary care medical center were searched for patients who underwent lung transplantation from 1997 to 2009 and acquired lung cancer postoperatively. The prevalence, potential contributing factors, and outcome of bronchogenic cancer were determined, and the medical literature was reviewed. RESULTS Bronchogenic cancer developed in 7 of the 290 lung transplant recipients (2.4%). All had received a single lung transplant and in most cases, the cancer developed in the native lung. These findings were similar to reports in the literature. The indication for transplantation was chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis/interstitial lung disease. All had a history of smoking. The average interval from transplantation to development of lung cancer was 5 years (range 1-9). Five patients had stage 4 cancer at diagnosis and 2 had stage 1. Six patients died from 10 days to 1 year after diagnosis. CONCLUSION Lung transplantation is associated with a relatively high prevalence of bronchogenic cancer, particularly in the native lung, in patients with primary chronic obstructive pulmonary disease/idiopathic pulmonary fibrosis, and a history of smoking. The cancer is usually diagnosed at an advanced stage with poor outcome. Efforts to improve screening are recommended, as aggressive management and treatment may be beneficial for earlier stage disease.

Long-term follow-up of flexible bronchoscopic treatment for bronchial carcinoids with curative intent.

Background. Typical pulmonary carcinoids represent less than 5% of primary lung tumors. In patients with typical bronchial carcinoid, formal surgical resection still remains the gold-standard treatment. Data regarding long-term outcome in using flexible bronchoscope-based modalities under conscious sedation is very limited. Objectives. We sought to investigate, over extended follow-up period, the effectiveness of endobronchial resection for carcinoid tumors with curative intent using flexible bronchoscopy. Methods. Nd:YAG laser photoresection using flexible bronchoscope under conscious sedation. Follow-up included repeat bronchoscopy every 6 months and chest CT every year. Results. Ten patients aged 24 to 70 years with endobronchial carcinoid were treated. The tumor location was variable: 2 left Main bronchus, 1 left upper lobe bronchus, 2 right main bronchus, 2 right middle lobe bronchus and 3 right lower lobe bronchus. No major complications were observed. The patients required between 2 and 4 procedures. Patients were followed for a median period of 29 months with no evidence of tumor recurrence. Conclusions. Endobronchial laser photoresection of typical bronchial carcinoids using flexible bronchsocopy under conscious sedation is an effective treatment modality for a subgroup of patients that provides excellent long-term results that are similar to outcome obtained by more invasive procedures.

Herpes zoster after lung transplantation: incidence, timing, and outcome.

BACKGROUND Although herpes zoster is a common complication of lung transplantation, the epidemiologic data are limited. The aims of the present study were to determine the incidence and clinical manifestations of herpes zoster in a large cohort of lung transplant recipients and to identify risk factors associated with its development. METHODS The files of all adult patients who underwent lung transplantation at a major tertiary medical center from January 2001 to December 2007 were reviewed. Data were extracted on background, transplant-related, and posttransplantation factors. The occurrence and clinical characteristics of all episodes of herpes zoster were recorded. RESULTS Of the 198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had herpes in a single dermatome. Disseminated cutaneous infection was documented in 4 cases (17%) and visceral involvement in 1. The median duration of follow-up was 34 months (range, 1 to 85 months). There were no recurrent infections. Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis, primarily for cytomegalovirus, was effective (during treatment) against herpes zoster. The incidence of herpes zoster was higher in patients treated with rabbit antithymocyte globulin. CONCLUSIONS The occurrence of herpes zoster peaks between 12 and 36 months after lung transplantation. Additional immunosuppression may increase the risk. Further studies on preventive strategies against herpes zoster in this population are warranted.

The lung in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common inflammatory disease, affecting about 1% of the population. Although a major portion of the disease burden including excess mortality is due to its extra-articular manifestations, the prevalence of RA-associated lung disease is increasing. RA can affect the lung parenchyma, airways, and the pleura; and pulmonary complications are directly responsible for 10 to 20% of all mortality. Even though pulmonary infection and drug toxicity are frequent complications of RA, lung disease directly associated with the underlying RA is more common. The prevalence of a particular complication varies based on the characteristics of the population studied, the definition of lung disease used, and the sensitivity of the clinical investigations employed. An overview of lung disease associated with RA is presented here with an emphasis on parenchymal lung disease, pleural effusion, and airway involvement.